Nanoparticle based oral delivery of vaccines: A promising solution for immunization challenges in developing nations: A comprehensive review

Most pathogens enter the body through mucosal sites, yet conventional needle-based vaccines primarily induce systemic immunity rather than mucosal protection at the pathogen entry point. Additionally, fear of painful injections deters many individuals from getting vaccinated. Another significant challenge for vast immunization campaign is the cold chain distribution logistics and the requirement of suitably trained health care workers. As a result, needle-free oral vaccines are gaining much attention due to their non-invasiveness, less stress and pain and better safety profile. These vaccines are cost-effective compared to injectable vaccines, as they simplify self-administration, reducing the need for qualified healthcare workers. This makes them ideal for large-scale vaccination coverage and improved occupational safety by preventing blood-borne disease risks. This makes them suitable for populations with limited access to trained professionals. Moreover, oral immunization stimulates mucosal immunity, providing protection at the infection entry site. However, oral vaccines face significant challenges from the harsh gastrointestinal (GI) environment, as most current vaccines (e.g., recombinant subunit, mRNA, DNA) are vulnerable to enzymatic and acid degradation. Additionally, the low permeability of the mucosal barrier and inefficient antigen uptake by antigen-presenting cells further hinder adequate immune stimulation. Thus, there is a need for safe and novel delivery methods to address emerging diseases. Nanoparticle encapsulation has emerged as a promising solution, offering potential for overcoming limitations in conventional drug delivery. This review explores nanoparticle-based oral vaccine delivery, covering nanoparticle types, limitations of traditional methods, recent advancements, and future prospects.